scholarly journals Activated melanoma vessels: A sticky point for successful immunotherapy

2020 ◽  
Vol 29 (11) ◽  
pp. 1046-1054
Author(s):  
Carsten Weishaupt ◽  
Tobias Goerge ◽  
Karin Loser
Keyword(s):  
Successful Immunotherapy

scholarly journals Pathways of immune exclusion in metastatic osteosarcoma are associated with inferior patient outcomes

2021 ◽  
Vol 9 (5) ◽  
pp. e001772
Author(s):  
John A Ligon ◽  
Woonyoung Choi ◽  
Gady Cojocaru ◽  
Wei Fu ◽  
Emily Han-Chung Hsiue ◽  
...  
Keyword(s):  
T Cell ◽  
Patient Outcomes ◽  
Immune Checkpoint ◽  
Tumor Antigens ◽  
Current Therapy ◽  
Normal Lung ◽  
Primary Bone Tumors ◽  
Metastatic Osteosarcoma ◽  
Immune Exclusion ◽  
Successful Immunotherapy

BackgroundCurrent therapy for osteosarcoma pulmonary metastases (PMs) is ineffective. The mechanisms that prevent successful immunotherapy in osteosarcoma are incompletely understood. We investigated the tumor microenvironment of metastatic osteosarcoma with the goal of harnessing the immune system as a therapeutic strategy.Methods66 osteosarcoma tissue specimens were analyzed by immunohistochemistry (IHC) and immune markers were digitally quantified. Tumor-infiltrating lymphocytes (TILs) from 25 specimens were profiled by functional cytometry. Comparative transcriptomic studies of distinct tumor-normal lung ‘PM interface’ and ‘PM interior’ regions from 16 PMs were performed. Clinical follow-up (median 24 months) was available from resection.ResultsIHC revealed a statistically significantly higher concentration of TILs expressing immune checkpoint and immunoregulatory molecules in PMs compared with primary bone tumors (including programmed cell death 1 (PD-1), programmed death ligand 1 (PD-L1), lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and indoleamine 2,3-dioxygenase (IDO1). Remarkably, these lymphocytes are excluded at the PM interface compared with PM interior. TILs from PMs exhibited significantly higher amounts of PD-1 and LAG-3 and functional cytokines including interferon-γ (IFNγ) by flow cytometry. Gene expression profiling further confirmed the presence of CD8 and CD4 lymphocytes concentrated at the PM interface, along with upregulation of immunoregulatory molecules and IFNγ-driven genes in the same region. We further discovered a strong alternatively activated macrophage signature throughout the entire PMs along with a polymorphonuclear myeloid-derived suppressor cell signature focused at the PM interface. Expression of PD-L1, LAG-3, and colony-stimulating factor 1 receptor (CSF1R) at the PM interface was associated with significantly worse progression-free survival (PFS), while gene sets indicative of productive T cell immune responses (CD8 T cells, T cell survival, and major histocompatibility complex class 1 expression) were associated with significantly improved PFS.ConclusionsOsteosarcoma PMs exhibit immune exclusion characterized by the accumulation of TILs at the PM interface. These TILs produce effector cytokines, suggesting their capability of activation and recognition of tumor antigens. Our findings suggest cooperative immunosuppressive mechanisms in osteosarcoma PMs including immune checkpoint molecule expression and the presence of immunosuppressive myeloid cells. We identify cellular and molecular signatures that are associated with patient outcomes, which could be exploited for successful immunotherapy.

Principles of successful immunotherapy

1991 ◽  
Vol 21 (s1) ◽  
pp. 216-220 ◽  
Author(s):  
Hans-Jorgen Mailing
Keyword(s):  
Successful Immunotherapy

scholarly journals Successful Immunotherapy against a Transplantable Mouse Squamous Lung Carcinoma with Anti–PD-1 and Anti-CD137 Monoclonal Antibodies

2016 ◽  
Vol 11 (4) ◽  
pp. 524-536 ◽  
Author(s):  
Arantza Azpilikueta ◽  
Jackeline Agorreta ◽  
Sara Labiano ◽  
José Luis Pérez-Gracia ◽  
Alfonso R. Sánchez-Paulete ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Lung Carcinoma ◽  
Transplantable Mouse ◽  
Successful Immunotherapy

scholarly journals Lymphoid infiltration as a predictor of successful immunotherapy with melanoma

2017 ◽  
pp. 61-66 ◽  
Author(s):  
K. S. TITOV ◽  
O. I. CHIKILEVA ◽  
M. V. KISELEVSKIY ◽  
A. M. KAZAKOV
Keyword(s):  
Lymphoid Infiltration ◽  
Successful Immunotherapy

Successful immunotherapy in a murine metastasizing fibrosarcoma model

1984 ◽  
Vol 25 (4) ◽  
pp. 289-295 ◽  
Author(s):  
Ruben Cortes ◽  
Luis A. Correa ◽  
Abdulla I. Behbehani ◽  
Stephen T. Sonis ◽  
Richard E. Wilson
Keyword(s):  
Successful Immunotherapy

scholarly journals A MAGE-C2 antigenic peptide processed by the immunoproteasome is recognized by cytolytic T cells isolated from a melanoma patient after successful immunotherapy

2011 ◽  
Vol 129 (10) ◽  
pp. 2427-2434 ◽  
Author(s):  
Wenbin Ma ◽  
Nathalie Vigneron ◽  
Jacques Chapiro ◽  
Vincent Stroobant ◽  
Catherine Germeau ◽  
...  
Keyword(s):  
T Cells ◽  
Melanoma Patient ◽  
Antigenic Peptide ◽  
Successful Immunotherapy
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